Combined and interactive effects of alcohol drinking and cigarette smoking on the risk of severe illness and poor clinical outcomes in patients with COVID-19: a multicentre retrospective cohort study.

OBJECTIVES: Cigarette smoking is an established risk factor for illness severity and adverse outcomes in patients with COVID-19. Alcohol drinking may also be a potential risk factor for disease severity. However, the combined and interactive effects of drinking and smoking on COVID-19 have not yet been reported. This study aimed to examine the combined and interactive effects of alcohol drinking and cigarette smoking on the risk of severe illness and poor outcomes in patients with COVID-19. STUDY DESIGN: This was a multicentre retrospective cohort study. METHODS: This study retrospectively reviewed the data of 1399 consecutive hospitalised COVID-19 patients from 43 designated hospitals. Patients were grouped according to different combinations of drinking and smoking status. Multivariate mixed-effects logistic regression models were used to estimate the combined and interactive effects of drinking and smoking on the risk of severe COVID-19 and poor clinical outcomes. RESULTS: In the study population, 7.3% were drinkers/smokers, 4.3% were drinkers/non-smokers and 4.9% were non-drinkers/smokers. After controlling for potential confounders, smokers or drinkers alone did not show a significant increase in the risk of severe COVID-19 or poor clinical outcomes compared with non-drinkers/non-smokers. Moreover, this study did not observe any interactive effects of drinking and smoking on COVID-19. Drinkers/smokers had a 62% increased risk (odds ratio = 1.62, 95% confidence interval: 1.01-2.60) of severe COVID-19 but did not have a significant increase in the risk for poor clinical outcomes compared with non-drinkers/non-smokers. CONCLUSIONS: Combined exposure to drinking and smoking increases the risk of severe COVID-19, but no direct effects of drinking or smoking, or interaction effects of drinking and smoking, were detected.

[Comparison of risk factors and short-term and long-term prognosis of pulmonary embolism between the Tibetan and Han people].

Objective: To compare the differences of risk factors and prognosis of pulmonary embolism (PE) between the Tibetans and the Hans. Methods: Patients over 18 years old with confirmed PE and complete clinical data from West China Hospital of Sichuan University from January 2010 to January 2016 were prospectively enrolled and divided into Tibetan group and Han group. Clinical data were collected to compare risk factors and short-term prognosis between Han group and Tibetan group. In addition, a 2-year follow-up was conducted among patients after discharge to investigate the long-term prognosis. Results: A total of 90 patients in Tibetan group and 626 patients in Han group were finally included in this study. Patients in Tibetan group were younger than Han group [(52.2±15.8) vs (59.8±16.6) years old, P<0.001], and the proportion of elderly patients (age ≥70 years) in Tibetan group was significantly lower than that of Han group (15.6% vs 33.7%, P=0.001). The hemoglobin, hematocrit, platelet counts and fibrinogen in Tibetan group were higher than those in Han group [(134.0±32.0) vs (122.2±25.7) g/L, (41.2±9.2)% vs (37.6±7.3)% and (222.2±97.5)×10(9)/L vs (187.5±87.2)×10(9)/L, 3.71(2.51, 4.89) vs 3.31(2.44, 4.42) g/L; P<0.001, <0.001 and P=0.001, 0.048, respectively]. Malignancy and chronic obstructive pulmonary disease were more common in Han group (P=0.011, 0.001), while prior venous thromboembolism history, pregnancy or a history delivery within 1 month were more common in Tibetan group (P=0.041, 0.001). Both short-term and long-term mortality in Tibetan group were significantly lower than that in Han group (2.2% vs 11.5%, 13.6% vs 24.9%; P=0.005, 0.020). Conclusions: Hypercoagulable state plays an important role in the pathogenesis of PE in Tibetan patients. Both short-term and long-term prognosis of PE in Tibetan patients are better than that in Han patients.

[Risk factors of pulmonary embolism in senile and non-senile inpatients and the predictive value of Caprini risk assessment model in these two populations].

Objective: To investigate the risk factors of pulmonary embolism (PE) in senile and non-senile inpatients, and evaluate the predictive value of Caprini risk assessment model in these two populations. Methods: Case control study design was used in this study. All the PE patients diagnosed in West China Hospital of Sichuan University between January 2012 and December 2014 was included and divided into senile PE group (age ≥65 years old) and non-senile PE group (age <65 years old). Age matched controls (senile control group and non-senile control group) were selected from the patients admitted into the same departments during the same time period as PE patients, at a ratio of 2∶1. The risk factors of PE for senile and non-senile inpatients were investigated through comparing senile or non-senile PE patients with corresponding controls. All the subjects were retrospectively evaluated by Caprini risk assessment model, and the associations between risk stratifications and PE risk were analyzed. Results: A total of 135 senile PE patients and 212 non-senile PE patients were finally included in this study, with average age of (73.58±6.66) years old and (45.60±13.11) years old, respectively. And 233 age-matched senile controls and 418 non-senile controls were also included. The multivariate analysis showed diabetes (OR=4.08, 95%CI: 1.58-10.51, P=0.004) , heart failure (OR=3.67, 95%CI: 1.10-12.20, P=0.034) , swollen legs (OR=10.50, 95%CI: 5.57-19.79, P<0.001) , severe lung disease (OR=2.05, 95%CI: 1.08-3.90, P=0.028) , patient confined to bed (>72 h) (OR=58.33, 95%CI: 7.46-456.17, P<0.001) were independent risk factors of PE in senile patients, while obesity[body mass index (BMI)≥25 kg/m(2)](OR=2.72, 95%CI: 1.42-5.24, P=0.003), history of deep venous thrombosis (DVT)/PE (OR=17.54, 95%CI: 2.74-112.19, P=0.002) , hip, pelvis, or leg fracture (OR=18.31, 95%CI: 1.97-170.11, P=0.011) , swollen legs (OR=18.53, 95%CI: 11.29-30.40, P<0.001) , severe lung disease ( OR=4.11, 95%CI: 2.41-7.00, P<0.001) , patient confined to bed (>72 h) (OR=4.04, 95%CI: 2.03-8.04, P<0.001) were independent risk factors of PE in non-senile patients. Among the senile patients, the risk of PE increased with the increase of Caprini risk levels; compared with Caprini moderate risk, classifications of high risk and highest risk were associated with 4.64-fold (95%CI: 1.05-20.44, P=0.043) and 10.74-fold (95%CI: 2.46-46.94, P=0.002) increased risk of PE, respectively; within the highest subgroup, the per 2-score increase of Caprini score was associated with 3.02-fold (95%CI: 1.76-5.19, P<0.001) increased risk of PE. Among those non-senile patients, the risk of PE for Caprini low risk and high risk patients was not significantly different, compared with Caprini moderate risk patients; however, the highest risk was still associated with 3.94-fold (95%CI: 2.39-6.51, P<0.001) increased risk of PE compared with moderate risk; within this subgroup, the per 2-score increase of Caprini score was associated with 2.13-fold (95%CI: 1.21-3.73, P=0.008) increased risk of PE. Conclusions: Swollen legs, severe lung disease, confined to bed (>72 h) are common PE risk factors among both senile and non-senile inpatients. Diabetes, heart failure are unique PE risk factors for senile inpatients, while obesity (BMI≥25 kg/m(2)), history of DVT/PE, hip, pelvis, or leg fracture are unique PE risk factors for non-senile inpatients. The Caprini risk assessment model has better predictive value in senile patients than non-senile patients, while Caprini highest risk classification is companied by significantly increased risk of PE in both populations.

[Risk factors of venous thromboembolism recurrence and the predictive value of simplified pulmonary embolism severity index in medical inpatients].

OBJECTIVE: To explore the risk factors of venous thromboembolism (VTE) recurrence and the predictive value of simplified pulmonary embolism severity index (sPESI) in medical inpatients. METHODS: A total of 149 consecutive patients with first diagnosed VTE from the medical departments of West China Hospital of Sichuan University from January 2011 and December 2012 were enrolled and followed-up for 24 months. The VTE recurrence rate was calculated and univariate and multivariate cox proportional hazards regression analysis were performed to identify the risk factors associated with VTE recurrence. All the patients were evaluated by sPESI, and survival analysis was used to explore its value in predicting VTE recurrence in these medical patients. RESULTS: Out of the included 149 patients, 23(15.4%) patients had VTE recurrence during the 2 years' follow-up and median recurrence time was 167 days. The univariate analysis showed bed rest, severe lung disease, nephrotic syndrome, inappropriate anticoagulant therapy, smoking, diabetes, and malignant neoplasm might be associated with VTE recurrence (P=0.043, 0.006, 0.009, 0.032, 0.098, 0.048, 0.021). Among these risk factors, the multivariate analysis revealed severe lung disease, nephrotic syndrome, and malignant neoplasm were the independent risk factors (HR=3.45, 5.67, 3.60; P=0.020, 0.020, 0.047); while for inappropriate anticoagulant therapy, the P value was marginal (HR=3.94, 95% CI: 0.99-15.63, P=0.051). The median sPESI scores of the patients with VTE recurrence was higher than that of the patients without VTE recurrence[1(1, 2) vs 0(0, 1), P=0.001], and patients with sPESI≥1 were associated with 5.57-fold increased risk of VTE recurrence compared with patients with sPESI=0 (95%CI: 1.79-17.30, P=0.001). Survival analysis also showed that the 2-year cumulative VTE recurrence rate of patients with sPESI≥1 was significant higher than that of patients with sPESI=0 (38.4% vs 5.7%, P=0.001). CONCLUSIONS: The medical VTE patients have high VTE recurrence risk, and severe lung disease, nephrotic syndrome, malignant neoplasm and inappropriate anticoagulant therapy are important risk factors of VTE recurrence. The sPESI has predictive value for VTE recurrence in medical patients.

Association of interleukin-1ß -511C/T promoter polymorphism with COPD risk: a meta-analysis.

Studies examining the role of interleukin (IL)-1ß -511C/T promoter polymorphism in the pathogenesis of chronic obstructive pulmonary disease (COPD) have shown inconsistent results. This meta-analysis was performed to assess the association between the IL-1ß-511C/T promoter polymorphism and COPD susceptibility. Published case-control, cross-sectional, and cohort studies from Pubmed, Embase, and China National Knowledge Infrastructure databases were retrieved. Data were extracted and pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Twelve studies with 1692 cases and 2009 controls were included in this meta-analysis. Pooled effect size showed an overall but not significantly decreased risk of IL-1ß-511 C/T with COPD susceptibility (OR = 0.89, 95%CI = 0.78-1.01) in a complete overdominant genetic model (TT+CC vs CT), indicating that homozygous individuals (CC and TT) have a decreased risk for COPD compared with heterozygotes (CT). In subgroup analysis by ethnicity, IL-1ß-511C/T was significantly correlated with a decreased risk of COPD in Asians (OR = 0.73, 95%CI = 0.60-0.88, P = 0.001), but not in Caucasians (OR = 1.02, 95%CI = 0.83- 1.24, P = 0.46), confirming a protective role of IL-1ß-511C/T in COPD in Asians. Moreover, after excluding studies that included populations not in Hardy-Weinberg equilibrium, the pooled results were robust and no publication bias was observed. This meta-analysis suggests that the IL-1ß-511C/T promoter polymorphism deceases the risk of COPD in Asians.

Temporal encoding and transmitting of amplitude and frequency modulations in dorsal cochlear nucleus.

Amplitude- and frequency-modulated (AM and FM, respectively) tones have been considered as simplified models of natural sounds. The responses of auditory neurons can phase-lock to the modulation frequency (fm). The encoding and transmitting of such modulation phase-locking are interesting since there is no any fm physical peak in spectrum. In the present study, we approached these issues by recording the phase-locked responses of the dorsal cochlear nucleus (DCN) units in guinea pigs to different AM and FM tones. For AM noise tones without the spectral cues of fm, the unit's discharges still phase-locked to the envelope cycles, but it was generally weaker than to sinusoidal AM (SAM) tones. At 50% modulation depth (dm), the mean modulation gains of Pauser/ Buildup (P/B) units (n = 7) to AM noise tones was -0.61 dB whereas they had a 6.48 dB mean to SAM tones. Similar to the case of AM tones, phase-locking to sinusoidal FM (SFM) tones represented the time courses of frequency changes, and it could be separated and changeable corresponding to the frequency increasing and decreasing. There were differences between the phase-locking to SAM and SFM tones in an identical unit. Both ON and type I/III units tended to have stronger phase-locking to the SFM tones than to the SAM tones. The phase-locking to the possible demodulated fm components was further examined with different carrier frequencies (fc) and pure tones. The DCN units showed poor or no responses to modulation tones out of their response areas even in the low characteristic frequency (CF) units, but the low-CF units had clear phase-locking to pure tones at the similar fm ranges. The puretone phase-locking had a band-pass shape different from the low-pass shape of the auditory nerve fibers. These data suggest that the modulation phase-locking in the DCN units may be based on the temporal modulation cues and transmitted in the carrier place. The temporal integration of modulation information over the unit's response area as an across-frequency temporal processing model was discussed for modulation enhancement in the CN units.

Processing of modulation frequency in the dorsal cochlear nucleus of the guinea pig: sinusoidal frequency-modulated tones.

Frequency- and amplitude-modulated (FM and AM, respectively) tones are important information-bearing elements in voice sounds and can also be produced by the spatial movement of sound sources. Zhao and Liang (1995) recently reported the response features of dorsal cochlear nucleus (DCN) neurons to AM tones. In the present study, the responses of the guinea pig DCN neurons to sinusoidal FM (SFM) tones were examined. Discharges of the DCN units to the SFM tones phase-locked to the stimulus modulation frequencies (fm). The phase-locked discharge patterns existed over broad ranges of modulation parameters and at stimulus levels as high as 95 dB SPL or modulation depths (dm) as low as 2%. Robust phase-locking to the fm was observed in samples of all DCN unit types studied. The means of best fm (Bfm) and upper limit fm (ULfm) of all recorded units were 510 Hz and 940 Hz, respectively. Pauser/Buildup (P/B) units had mean maximum synchronization index (SImax) of 0.57. ON units had the highest Bfm with the mean of 646 Hz and subtype ON-S showed the highest mean of SImax at 0.63. Phase-locking to the fm was independent of discharge rates and existed even when the discharge rates were reduced to the background spontaneous rate (SR). A few units showed stronger synchronous responses to the square and triangular FM stimuli instead of the SFM tones. The relationship between the modulated responses and the unit's response area were further examined. The fm phase-locking occurred to modulation bands (or frequency ranges) within the response area, with the modulation bands as narrow as +/- 160 Hz in the central inhibitory areas of the type IV units. As the width of the modulation band changed within a unit's response area, the phases of the fm phase-locked responses of P/B units linearly changed while for Onset units, the change was lesser. The P/B and Onset units had a pi phase shift and a pi/2 phase change, respectively, as carrier frequencies (fc5) passed through characteristic frequencies (CF) and the excitatory/inhibitory response boundaries. The phase-locked responses to the fms were dependent on the SR but were independent of the CF. Low-SR (< or = 2 spikes/s) units had higher synchronization of responses to the fm than the high-SR (> 2 spikes/s) units (SImax = 0.64 and 0.42 respectively). These results suggest that the temporal characteristics of the fm is effectively represented in the responses of DCN units to the SFM tones. Such temporal encoding behavior can play an important role in the processing of the complex sounds in the auditory system. These results also have implications for a possible role for the DCN is in identifying the spatial movement of a sound source.

Processing of modulation frequency in the dorsal cochlear nucleus of the guinea pig: amplitude modulated tones.

The modulation frequency (Fm), particularly high Fm (> 200 Hz), in amplitude modulated (AM) tones can elicit the perception of the periodicity pitch (Langner, 1992). In this study, single unit responses to the Fms of the sinusoidal AM tones were investigated at 50 to 90 dB SPL. The recordings were made from the dorsal cochlear nucleus (DCN) of neuroleptic anesthetized guinea pigs with an intact cerebellum. The DCN units show a good capability of phase-locking to Fm at 400-1200 Hz. On-S-type II and Pauser/Buildup (P/B) units have a high modulation gain (7.2-8.3 dB). P/B units can preserve the high modulation gain (5-9 dB) up to 90 dB SPL. The modulation gain exponentially increases with decreasing modulation depth (Dm) and the phase-locking is detectable even at the Dm as low as 2-5%. The 'central skipping' of the phase-locking peak has been found at deep Dms in a few cases. The synchronization is independent of the discharge rate and can remain high even when the responses to AM tones are inhibited below the spontaneous activity. Such encoding behaviors over the unit's response area show that the Fm phase-locking is strong near or at its characteristic frequency (CF). The synchronization index (SI) versus carrier frequency (Fc) curve is similar to the inverse shape of tuning curve but more narrowly tuned than the iso-intensity function of pure tones at moderate to high intensity levels. The phase-locking is related to the unit's spontaneous rate (SR). The average modulation gain of the lower SR (< or = 2 spikes/s) units is 5 dB higher than that of the higher SR (> 2 spikes/s) units (8.16 and 2.92 dB, respectively) at 70 dB SPL. These results suggest that AM information is temporally encoded over broad ranges of modulation parameters in the DCN and is conveyed by the Fc channel. Such a timing mechanism can play an important role in processing of complex sounds under normal acoustic conditions.